Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease.

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56-positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16(+)-positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T-cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.     

Use of calcium alginate to pack abscess cavities: a controlled clinical trial.

Many conventional dressings are painful when removed, and may be detrimental to healing. In a pilot study ten consecutive abscesses, requiring incision and drainage, were packed with a calcium alginate dressing: this was well tolerated, its removal causing minimal pain. No adverse effects were attributable to its use. A controlled trial was therefore carried out to compare calcium alginate with the more traditional saline-soaked gauze for packing abscess cavities, following incision and drainage. Patients were randomized to receive either calcium alginate (16 patients) or gauze dressing (18 patients). At the first dressing change the patient marked on a linear analogue scale the pain experienced; the nurse noted similarly the ease of removal of the dressing. Calcium alginate was significantly less painful to remove after operation (P less than 0.01), and also easier to remove (P less than 0.01) than gauze dressings. If abscess cavities are packed after incision and drainage, calcium alginate appears to be an improvement on conventional dressings.     

Immunity after treatment of human schistosomiasis: association between cellular responses and resistance to reinfection.

Previous studies have demonstrated the development of an age-dependent resistance to reinfection after chemotherapeutic cure of the helminthic parasite Schistosoma mansoni. Here we report on a longitudinal investigation of cell-mediated responses in infected individuals before and after treatment which was designed to outline those parameters important in mediating a protective response. A well-defined study group of 89 individuals with an age range of 9 to 35 years was selected from an area of high S. mansoni transmission in the Machakos district of Kenya. Peripheral blood mononuclear cell proliferation and cytokine production (interleukin-2 [IL-2], gamma interferon IL-5, IL-4, and tumor necrosis factor) in response to different crude life cycle-stage antigens of S. mansoni were assessed longitudinally in vitro before, 3 months after, and 1 year after treatment. Detailed statistical analyses of the results from this study have indicated a clear negative association between the proliferative responses to adult- and schistosomulum-stage antigens and subsequent reinfection intensity in older individuals (14 to 35 years) which was not present in the younger individuals (9 to 13 years). This association was significant even after the effects of age, sex, and exposure had been accounted for in multiple regression analyses. Cytokines were detected predominantly in response to adult worm and egg antigen extracts. An inverse association between the two cytokines gamma interferon and IL-5 was detected in response to all antigens at the three time points investigated, indicating cross-regulation in the production of these two mediators. Differences in antigen-specific cytokine levels between the two age groups were detected, with significantly higher IL-5 levels detected in the older (more resistant) age group. An inverse correlation between this cytokine and reinfection was detected but could not be dissociated from the effects of age and exposure in multiple regression analysis.     

Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast

AIMS: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation. METHODS: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined. RESULTS: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p=0.0005). CONCLUSIONS: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.     

Center for disease control diagnostic immunology proficiency testing program results for 1976.

Over 900 laboratories participated in the Diagnostic Immunology portion of the 1976 Proficiency Testing Program, which was provided by the Center of Disease Control under the authority of the Clinical Laboratories Improvement Act of 1967. One hundred specimens prepared by the Center for Disease Control for analysis were distributed on a quarterly schedule or in special surveys. Feedback from participating laboratories included over 37,500 qualitative and 33,000 quantitative responses, which were analyzed to determine individual laboratory proficiency levels. In addition, information supplied by participants in each survey helped to delineate trends in testing protocols. The specimens chosen for analysis called for a broad range of tests commonly performed in diagnostic immunology laboratories, including those for rubella antibodies, hepatitis B surface antigen, bacterial antibodies, rheumatoid factor, immunoglobulins and other serum-specific proteins, and carcinoembryonic antigen. A summary of the data analysis is provided so that the laboratories can improve their overall performance levels.     

Fifty-year mortality trends in three rural African villages

OBJECTIVE: To determine differential improvements in mortality rates according to age, and to discuss differences in neonatal and post-neonatal mortality rates, using longitudinal data from the past 50 years in three rural Gambian villages. METHODS: All villagers whose date of birth was recorded were followed up until death or October 1997. A Lexis expansion was performed to categorize age: early neonatal, late neonatal, infant, 1-4 years, 5-14 years and 15 or more years. Calendar time was divided into three periods -- prior to 1975, 1975-1984 and after 1985, representing different levels of clinical care. Cox regression and likelihood-ratio test were used to model the hazards ratios. RESULTS: There were 3981 subjects included in the analysis with a total of 59 002 person-years follow-up. There was a dramatic decrease in neonatal (44 to 15), infant (162 to 36) and under-five mortality rates (397-66 per 1000) from pre-1975 to the present. The disproportionate decrease in the mortality rates means that neonatal deaths accounted for a greater percentage of post-natal deaths in later years. There was a marked seasonality in mortality rates with significantly more deaths in the 'hungry' season prior to 1975 (odds = 1.87; 95% CI = 1.62-2.17) and from 1975 to 1984 (odds = 1.84; 95% CI = 1.34-2.53). This seasonality of death has diminished in recent years (odds = 1.23; 95% CI = 0.85-1.76). CONCLUSION: Our analysis indicates a dramatic reduction in mortality rates and an attenuation in the seasonality of death. It is likely that the efficient implementation of basic currently available health measures was one of the key elements in achieving such a major reduction in mortality.     

Juvenile rhesus monkeys have lower type 2 cytokine responses than adults after primary infection with Schistosoma mansoni

Adults and children have differences in their susceptibility to schistosomiasis. The relative influences of age-dependent innate resistance and acquired immunity in the differences between susceptibility to schistosomiasis are difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. In contrast to the adult animals, the juvenile rhesus monkeys had low levels of interleukin (IL)-4 and IL-5 production by peripheral blood mononuclear cells after schistosome infection, as well as lower levels of parasite-antigen-specific antibody (IgG, IgM, and IgA) responses, and produced limited antigen-specific or total IgE. Juvenile animals had statistically nonsignificant increased worm burdens and tissue or fecal egg counts, compared with that of adults, whereas circulating schistosome antigens were significantly higher in infected juvenile monkeys. These results suggest that juvenile rhesus monkeys have reduced type 2 cytokine responses after primary schistosome infections and perhaps are more susceptible to parasite infection.     

An intact dopaminergic system is required for context-conditioned release of 5-HT in the nucleus accumbens of postweaning isolation-reared rats

We investigated the effect of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT) on extracellular dopamine and 5-HT levels in the nucleus accumbens of group- and isolation-reared rats. Microdialysis with high-performance liquid chromatography-electrochemical detection was used to quantify dopamine and 5-HT efflux in the nucleus accumbens following foot shock and in association with a conditioned emotional response (CER). Isolation- and group-reared rats received i.p. injections of either saline (0.9%) or AMPT (200 mg/kg) 15 h and 2 h prior to sampling. There was no significant difference between saline-treated isolation- or group-reared rats for basal efflux of dopamine or 5-HT, however as expected, AMPT-treatment significantly reduced dopamine efflux in both groups to an equivalent level (50-55% saline-treated controls). Exposure to mild foot shock stimulated basal dopamine efflux in saline-treated groups only, although the effect was significantly greater in isolation-reared rats. In AMPT-treated rats, foot shock did not affect basal dopamine efflux in either rearing group. Foot shock evoked a prolonged increase in 5-HT efflux in both isolation- and group-reared saline-treated rats but had no effect on 5-HT efflux in AMPT-treated rats. In response to CER, isolation-rearing was associated with significantly greater efflux of both dopamine and 5-HT in saline-treated rats, compared to saline-treated, group-reared controls. However in AMPT-treated rats, efflux of dopamine or 5-HT did not change in response to CER. These data suggest that unconditioned or conditioned stress-induced changes in 5-HT release of the nucleus accumbens are dependent upon intact catecholaminergic neurotransmission. Furthermore, as the contribution of noradrenaline to catecholamine efflux in the nucleus accumbens is relatively minor compared to dopamine, our findings suggest that dopamine efflux in the nucleus accumbens is important for the local regulation of 5-HT release in this region. Finally, these findings implicate the isolation-enhanced presynaptic dopamine function in the accumbens with the augmented ventral striatal 5-HT neurotransmission characterized by isolation-reared rats.